Related Experiment Video

Updated: Jul 29, 2025

Rating L-DOPA-Induced Dyskinesias in the Unilaterally 6-OHDA-Lesioned Rat Model of Parkinson's Disease
06:45

Rating L-DOPA-Induced Dyskinesias in the Unilaterally 6-OHDA-Lesioned Rat Model of Parkinson's Disease

Published on: October 4, 2021

2.8K

Striatal CDK5 Regulates Cholinergic Neuron Activation and Dyskinesia-like Behaviors through BK Channels

Chu Tong1, Peng-Xiang Min2, Qian Zhang1

  • 1Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, 211166, China.

Research (Washington, D.C.)
|May 24, 2023
PubMed

Insights

Reduced cyclin-dependent kinase 5 (CDK5) in cholinergic neurons contributes to neurological diseases like Parkinson's. This study reveals CDK5's role in regulating motor function via BK channels, offering a potential therapeutic target.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Cholinergic system dysfunction is implicated in neurological diseases causing dyskinesia-like behaviors.
  • The precise molecular mechanisms behind this cholinergic disturbance are not fully understood.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase 5 (CDK5) in cholinergic neurons and its impact on motor function.
  • To elucidate the molecular targets and pathways through which CDK5 influences motor control and dyskinesia.

Main Methods:

  • Single-nucleus RNA sequencing to identify changes in gene expression in midbrain cholinergic neurons.
  • Assessment of motor behaviors, neuronal excitability, and ion channel activity in mouse models with altered CDK5 levels.
  • Biochemical assays to determine the interaction and regulatory relationship between CDK5 and BK channels.

Main Results:

  • CDK5 levels were reduced in midbrain cholinergic neurons and serum of Parkinson's disease patients.
  • Cdk5 deficiency in cholinergic neurons led to motor deficits (tremors, impaired coordination) and neuronal hyperexcitability.
  • CDK5 negatively regulates large-conductance Ca2+-activated K+ (BK) channels via phosphorylation, impacting neuronal excitability.
  • Inhibition of BK channels ameliorated motor deficits in Cdk5-deficient mice.
  • Restoring CDK5 expression reduced dyskinesia-like behaviors.

Conclusions:

  • CDK5 plays a critical role in regulating motor function by modulating BK channel activity in cholinergic neurons.
  • The CDK5-BK channel pathway represents a potential therapeutic target for treating dyskinesia-like behaviors in neurological disorders.

More Related Videos

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke07:00

Excitotoxic Stimulation of Brain Microslices as an In vitro Model of Stroke

Published on: February 4, 2014

8.5K
Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting10:08

Study of the Functions and Activities of Neuronal K-Cl Co-Transporter KCC2 Using Western Blotting

Published on: December 9, 2022

2.2K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
722
Neural Regulation01:37

Neural Regulation

Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
39.6K
Direct-Acting Cholinergic Agonists: Pharmacokinetics01:31

Direct-Acting Cholinergic Agonists: Pharmacokinetics

Direct-acting cholinergic agonists, such as synthetic choline esters and naturally occurring alkaloids, exert their effects by enhancing the actions of acetylcholine and stimulating the parasympathetic nervous system. Synthetic choline esters share structural similarities with acetylcholine. For example, they have a positively charged quaternary ammonium or onium group, contributing to their hydrophilic characteristics. As a result, they are poorly absorbed in the body through oral...
1.3K
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K
Indirect-Acting Cholinergic Agonists: Mechanism of Action01:18

Indirect-Acting Cholinergic Agonists: Mechanism of Action

Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.9K